Digital Membrane Chromatography — A New Way to Rapid Antibody Purification for Top-Down Mass Spectrometry

Antibody purification is essential for both large-scale manufacturing and analytical workflows. However, conventional Protein A affinity chromatography often relies on acidic elution buffers that can compromise structural integrity and require extensive post-elution processing for mass spectrometry (MS). In this work, we present a novel Protein A (DMCPrA) membrane adsorber, which employs a Protein A-functionalized regenerated cellulose membrane integrated with conductive gold-coated layers to enable voltage triggered elution. This new technology is called Digital Membrane Chromatography (DMC). Using Trastuzumab as a model, we demonstrate that DMCPrA enables efficient antibody capture and gentle MS-compatible elution, eliminating the need for time-consuming desalting or buffer exchange. The approach preserves structural integrity, supports analysis from complex matrices, and shortens processing times compared to conventional workflows.